依那普利抑制大鼠血管平滑肌细胞表型转化及可能的信号通路

doi:10.6040/j.issn.1671-7554.0.2015.778

山东大学学报（医学版） ›› 2016, Vol. 54 ›› Issue (2): 21-26.doi: 10.6040/j.issn.1671-7554.0.2015.778

依那普利抑制大鼠血管平滑肌细胞表型转化及可能的信号通路

杨博^1,2,李平¹,孟立平^2,3,周昌钻^2,3,潘孙雷^2,3,池菊芳²,郭航远^2,3

1.山东能源新汶矿业集团莱芜中心医院心内科, 山东莱芜 271103;2.绍兴市人民医院心内科, 浙江绍兴 312000;3.温州医科大学研究生学院, 浙江温州 325000

收稿日期:2015-08-18 出版日期:2016-02-10 发布日期:2016-02-10
通讯作者: 郭航远. E-mail:ghangyuan8@sina.com E-mail:ghangyuan8@sina.com
基金资助:
浙江省自然科学基金(LY14H020002);浙江省公益技术研究社会发展(2012C33040);绍兴市科技局(2013B70072)

Enalapril inhibits homocysteine-induced smooth muscle cell dedifferentiation and its signal pathway

YANG Bo^1,2, LI Ping¹, MENG Liping^2,3, ZHOU Changzuan^2,3, PAN Sunlei^2,3, CHI Jufang², GUO Hangyuan^2,3

1. Department of Cardiology, Laiwu Central Hospital of Shandong Energy Xinwen Mining Group, Laiwu 271103, Shandong, China;
2. Department of Cardiology, Shaoxing Peoples Hospital, Shaoxing 312000, Zhejiang, China;
3. Wenzhou Medical University, Wenzhou 325000, Zhejiang, China

Received:2015-08-18 Online:2016-02-10 Published:2016-02-10

摘要/Abstract

摘要： 目的探讨依那普利是否具有抑制同型半胱氨酸(Hcy)诱导的大鼠血管平滑肌细胞(VSMCs)表型转化的作用及其可能的信号通路。方法 SD大鼠主动脉VSMCs原代细胞培养鉴定,取4~7代VSMCs分为对照组、100 μmol/L 同型半胱氨酸组、同型半胱氨酸+依那普利干预组和Hcy+LY-294002干预组。采用MTT法检测各组VSMCs的增殖情况;采用划痕法和Transwell法检测各组VSMCs的迁移情况;ICC法观察各组VSMCs的细胞形态;采用Western blotting法检测各组VSMCs中SM-actin、SM-MHC、calponin、OPN和pAKT的表达。结果与对照组相比,同型半胱氨酸组VSMCs增殖迁移增加,细胞形态变圆,SM-MCH和calponin表达减少(P<0.01),OPN和p-AKT表达增加(P<0.01)。与Hcy组相比,依那普利组和LY-294002组VSMCs增殖和迁移减少,细胞形态变得细长,SM-MHC和Calponin表达增加(P<0.01);OPN和pAKT表达减少(P<0.01)。结论 Hcy可以促进VSMCs表型转化,依那普利可以抑制Hcy诱导的VSMCs表型转化,其机制可能是通过抑制PI3K/p-AKT途径实现。

关键词: 依那普利, 平滑肌细胞表型转换, LY-294002, 同型半胱氨酸

Abstract: Objective To explore whether enalapril could inhibit homocysteine(Hcy)-induced dedifferentiation of rat aortic vascular smooth muscle cells(VSMCs)and its potential mechanism. Methods The primary culture and identification of rat VSMCs was conducted and VSMCs in passage 4-7 were divided into 4 groups: control group, Hcy(100 μmol/L)group, Hcy+enalapril group, and Hcy+LY-294002 group. The proliferation and migration of VSMCs were detected using MTT, transwell chambers and wound healing, respectively. The morphology of VSMCs was observed with ICC. The expressions of SM-actin, SM-MHC, Calponin, OPN and p-AKT in VSMCs of every group were investigated using Western blotting. Results Compared with those of the control group, the proliferation and migration ability of VSMCs were significantly increased, the expressions of SM-MCH and Calponin were increased, while OPN was decreased in the Hcy group(P<0.01). There was no significant difference in the expression of SM-actin 山东大学学报 (医学版)54卷2期 -杨博,等.依那普利抑制大鼠血管平滑肌细胞表型转化及可能的信号通路 \=-among the groups. Compared with those of the Hcy group, the proliferation and migration ability of VSMCs were significantly decreased, the expression of SM-MCH and calponin increased, while OPN and pAKT expressions were decreased in enalapril and LY-294002-treated groups(all P<0.01). Conclusion Hcy can induce, while enalapril can inhibit the dedifferentiation of VSMCs, by inhibiting the PI3K/p-AKT signal pathway.

Key words: Vascular smooth muscle cell dedifferentiation, LY-294002, Enalapril, Homocysteine

中图分类号:

R543.3

杨博,李平,孟立平,周昌钻,潘孙雷,池菊芳,郭航远. 依那普利抑制大鼠血管平滑肌细胞表型转化及可能的信号通路[J]. 山东大学学报（医学版）, 2016, 54(2): 21-26.

YANG Bo, LI Ping, MENG Liping, ZHOU Changzuan, PAN Sunlei, CHI Jufang, GUO Hangyuan. Enalapril inhibits homocysteine-induced smooth muscle cell dedifferentiation and its signal pathway[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(2): 21-26.

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依那普利抑制大鼠血管平滑肌细胞表型转化及可能的信号通路

Enalapril inhibits homocysteine-induced smooth muscle cell dedifferentiation and its signal pathway

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